The burden of comorbid diseases is high among patients with rheumatoid arthritis (RA). These are often systemic manifestations of RA but may be chronic conditions that predate or develop post-RA diagnosis. Increased mortality in RA is predominantly from nonarticular causes. The expanded armamentarium of disease-modifying drugs and biologics available has revolutionized management of articular disease but has made safe treatment of RA more complex. Drug-induced organ injury and side effects need to be kept in mind when initiating or modifying therapy.