Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are chronic, systemic, autoimmune disorders characterized by inflammatory processes. There are numerous classes of therapies available to treat RA and IBD, and some patients achieve low disease activity or remission, yet a proportion of patients exhibits an inadequate response and/or discontinues therapy due to tolerability. As such, investigations into new targets and therapies, such as the janus kinase (JAK) inhibitors, continue. The introduction of JAK inhibitors further contributes to a growing armamentarium of therapies for these immune-mediated inflammatory diseases. Evolving strategies for employing the JAK inhibitors present a decision-making challenge to clinicians who treat these patients.