Ovarian cancer is the leading cause of gynecological cancer-associated deaths in developed countries. In the United States, ovarian cancer is the fifth leading cause of cancer death in females, with an estimated incidence of 14,180 deaths in 2015 [
1]. High-grade serous ovarian cancer (HGSOC) accounts for 70–80 % of ovarian cancer deaths. While this disease is termed an ovarian cancer, a wide range of studies have suggested that secretory epithelial cells of the distal fallopian tube are the likely progenitors of a substantial proportion of HGSOCs, although some HGSOCs arise without fallopian tube [
2]. While the survival rates of patients diagnosed with early stage ovarian cancer are high, most cases are diagnosed at a late stage with peritoneal dissemination. If diagnosed at an early stage, the 5-year survival rate exceeds 90 %. However, in patients with stage III or IV ovarian cancer, despite comprehensive treatments by aggressive cytoreductive surgery and chemotherapy with platinum- and taxane-based drugs, the 5-year survival rate remains at a dismal 30 % [
1]. This high mortality rate of ovarian cancer is associated with the difficulties of early detection, because it is usually asymptomatic until late stage. Efficient early detection procedures have yet to be established. Although pelvic examination, transvaginal ultrasonography, and serum carbohydrate antigen 125 (CA125) are usually performed as routine diagnostic procedures for ovarian cancer, their diagnostic values are limited due to lack of the sensitivity and specificity [
3]. For example, CA125 is only elevated in 50–60 % patients with stage I and II ovarian cancer [
4]. In the retrospective study with 751 females, the sensitivity of CA125 for ovarian cancer at all stages was 88.6 %, but with a specificity of only 72.0 % [
4]. In the recent study with 118 patients with ovarian cancer, 84 with benign disease, and 61 healthy females, the sensitivity and specificity of CA125 were 77.4 and 70.8 %, respectively [
5]. Therefore, development of novel approaches to effectively detect ovarian cancer at an early, curable stage is urgently required. Another cause of this high mortality rate is the resistance to chemotherapy, especially in recurrent cases. Although ovarian cancer is highly responsive to the initial treatment by platinum- and taxane-based chemotherapies, subsequent relapses and repeated treatments using these cytotoxic chemotherapies eventually result in acquired resistance to the treatments. Therefore, most patients who experience cancer relapse eventually succumb to the disease [
6]. In the last decade, a variety of targeted therapies have been developed to target the cancer-specific genes and proteins or the tumor microenvironment that contributes to cancer growth and maintenance. Among the new drugs studied for ovarian cancer, bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has shown promising activities in combination with standard chemotherapies in large Phase III trials [
7,
8]. However, no significant benefits with respect to overall survival have been reported so far. Poly ADP ribose polymerase (PARP) inhibitors, which lead to formation of extensive double-stranded DNA breaks that cannot be accurately repaired in tumors, have shown potential for improved survival. Olaparib, a potent oral PARP inhibitor, significantly improved progression-free survival in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer; however, interim analysis showed no overall survival benefit [
9]. Therefore, definitive treatments that substantially extend overall patient survival have yet to be established [
10]. This is partly due to the lack of methods to discriminate between patients who will or will not benefit from the specific molecular targeted treatments. Thus, identification of useful clinical biomarkers to predict possible resistance to each treatment and prognoses of cancer patients would greatly benefit the management of ovarian cancer treatment [
11]. Accumulating evidence has revealed that microRNAs (miRNA or miR) are extensively involved in cancer progression and suppression by regulating thousands of cancer-associated genes [
12]. miRNAs can stably exist not only in cytoplasm, but also in various types of body fluids. Circulating cell-free miRNAs have been shown to have the potential to enable earlier cancer diagnosis and to predict prognosis and response to therapy [
13]. This review summarizes the cumulative efforts in the field of circulating miRNAs focusing on their potential as novel biomarkers in ovarian cancer.