In this review, we highlight research into the therapeutic potential of KOR agonists within key diseases including nociception (Paton et al., 2017), pruritis (Wang et al., 2021), multiple sclerosis (MS) (Denny et al., 2021), Alzheimer’s disease (AD) (Song et al., 2021), immune mediated diseases such as osteoarthritis (Wilson et al., 1996), atopic dermatitis (Nakasone et al., 2015), food allergy (Duncker et al., 2012), gastrointestinal diseases (Mangel et al., 2008), cancer (Yamamizu et al., 2013), and hypoxia and ischemia (Wu et al., 2021). Here, OPRK1 is linked to multiple sclerosis.