Rosacea is a chronic inflammatory skin disease affecting primarily the cheeks, nose, chin, and forehead [
1]. It has been generally classified into four clinical subtypes, of which the erythematotelangiectatic subtype is most common followed by the papulopustular subtype [
28,
30,
31]. Since subtypes frequently overlap and can vary over time, a phenotype approach is now recommended by an international ROSacea COnsensus (ROSCO) panel, the National Rosacea Society, and the American Acne and Rosacea Society in recognition of the inaccuracies and limitations of subtyping [
29]. The prevalence of rosacea varies greatly between countries and has been reported to range from less than 1% to 22% [
28]. Most frequently, women between 30 and 50 years of age are affected, although rosacea is also common among men [
8]. Rosacea can negatively affect both social and professional life and is linked to depression, anxiety, and low self-esteem [
3,
7,
12,
16]. Although the pathophysiology of papulopustular rosacea is not fully understood, the first experimental study in vivo demonstrated a potentially important role for
Demodex folliculorum [
21]. Although these mites are part of the normal cutaneous microflora, it has been shown that the cutaneous density of
Demodex mites in patients with rosacea is increased [
9‐
11,
32]. Recently, it has been demonstrated that
Demodex mites have the capacity to downregulate the Toll-like receptor-2 (TLR-2) response to facilitate their survival [
15]. In contrast, when present in increased numbers,
Demodex mites activate a TLR-2 pathway immune response. This results in the release of pro-inflammatory mediators leading to inflammatory skin changes [
13,
15]. Established treatment options, including topical metronidazole, azelaic acid, and tetracyclines, are thought to work through their anti-inflammatory but not through their antimicrobial effects. However, none of these therapies have been shown to be curative and are associated with frequent relapses, even during treatment [
35]. Therefore, new and improved treatment options are needed. Ivermectin was originally used as an oral anti-parasitic drug and has a dual mechanism of action, having both anti-inflammatory and acaricidal activity against
Demodex mites [
14,
21]. Thus, topical ivermectin might pave the way to a more etiologic treatment of papulopustular rosacea with less frequent relapses. Thus, its use is now widely propagated in mild-to-severe papulopustular rosacea [
21,
22]. However, current clinical guidelines have yielded different treatment algorithms and, in some areas, conflicting recommendations [
2,
22,
1]. The objective of this systematic review is to critically appraise current evidence and guideline recommendations for the use of topical ivermectin in papulopustular rosacea.