Musculoskeletal injuries are classified as any injury that affects bones, muscles, ligaments, tendons, and nerves [
1]. These ailments bring pain to millions of people each year and costs healthcare services an estimated $54 billion every year [
2]. Current and conventional methods of treatment for such conditions are limited, as they often do not address the pathology that initially caused the damage [
3‐
5]. Presently, non-surgical methods for the relief of orthopaedic injuries include lifestyle changes such as exercise, diet, physical therapy, and weight loss [
6‐
9]. Other treatments involve non-steroidal anti-inflammatory drugs (NSAIDs), viscosupplementation, corticosteroid injections, and opioids [
6,
10‐
12]. NSAIDs do aid the patient’s pain in the short-term, but do not address the underlying problem [
13]. In viscosupplementation, hyaluronic acid is injected into a patients joint. This hyaluronic acid is supposed to act as a lubricant and reduce discomfort and facilitate movement, but many patients do not necessarily experience an improvement in their function [
6]. Corticosteroid injections can also help reduce inflammation and pain [
14], but they only provide interim relief [
14]. Parenteral and epidural opioids are relatively effective in relieving postoperative pain, but orthopaedic surgeons have many hesitations to prescribe them [
15]. For example, mild side effects for opioid medications include constipation, sedation, and vomiting, and more severe adverse effects entail hypertension, respiratory problems, urinary difficulties, and dehydration [
15]. Furthermore, a major cause for concern when prescribing opioids for pain management is the potential for a patient to develop dependence on the drug [
15]. While all these treatment methods are somewhat beneficial, they all seem to be temporary solutions to the patient’s underlying problem. In response to these limitations, researchers and clinicians have shown increased interest in the use of regenerative medicine-based modalities [
16‐
19]. These regenerative medicine modalities include autologous and allogenic sources. The main types of autologous treatments include platelet-rich plasma (PRP) injections, bone marrow transplants (BMTs), and the use of adipose-derived tissues (ADTs) and/or cells (ADCs) [
20‐
23]. Although promising, these autologous sources have limitations. For example, the efficacy of PRP injections is highly variable, as basic science research studies show that their effects can be both pro- and anti-inflammatory and the therapeutic results depend on several factors [
24]. BMT, or hematopoietic stem cell transplantation, also presents its own limitations, as patients were more likely to experience post-operative complications compared to patients who underwent an allogenic BMT [
25]. One of the most common means of obtaining ADT or ADCs for autologous treatment is via stromal vascular fraction (SVF). SVF is an accessible, minimally manipulated array of cells that can be used for autologous regenerative treatment [
26], which can be isolated either enzymatically or mechanically [
27]. Although this is a promising method, there is a dearth of randomized controlled studies for orthopaedic conditions [
28]. Additionally, autologous transplants are susceptible to the relapse of tumor if the autograft contains malignant cells [
29]. Autologous ADTs/ADCs and BMTs pose may carry point of harvest morbidity [
30‐
32]. To overcome these limitations, and develop an alternate supply, clinicians have begun exploring the use of allogenic sources bypassing some of the drawbacks associated with autologous tissue/sources. The allogenic perinatal tissues discussed in this article include the amnion/chorion membrane (ACM), amniotic fluid (AF), umbilical cord (UC), umbilical cord-derived Wharton’s jelly (UC-WJ), and mesenchymal stromal/stem cells (MSCs) derived from these tissues. There is ample literature showing the safety and efficacy of autologous sources, but there is limited research concerning perinatal allogenic sources. This review aims to document the preclinical and clinical outcomes of different perinatal allogenic tissues and/or derived cells for orthopaedic regenerative medicine applications. The secondary goal is to list all ongoing clinical trials enlisted on ClinicalTrials.gov related to different perinatal allogenic tissues and/or derived cells for orthopaedic regenerative medicine applications.