Janus kinase inhibitors (JAKi) are orally active small molecules that block intracellular JAK–STAT signalling and have transformed treatment of several immune-mediated diseases. This paper summarizes the pharmacology and selectivity of marketed JAKi, evidence of efficacy across major autoimmune indications (rheumatoid arthritis, psoriatic disease, atopic dermatitis, and ulcerative colitis), major safety signals from long-term and large safety trials, regulatory actions, practical monitoring, and how clinicians can position JAKi within contemporary treatment algorithms. Key randomized trials, long-term extension, and safety studies are synthesized to provide balanced clinical guidance.