New guidelines for osteoarthritis, low back pain, and other conditions feature recommendations that impact and prioritize NSAID utilization. NSAIDs have been a cornerstone of pain management of inflammatory, connective tissue, and autoimmune disorders for more than 100 years. A historical perspective is key to understanding the role of NSAIDs in pain management, and a therapeutic update on current evidence will aid providers in practical utilization. The safety of NSAIDs will be reviewed and compared to risks of other medications including opioids. FDA warnings on cardiovascular risk of NSAIDs will be placed into context and examples of clinical decision-making provided. In addition, new formulations of NSAIDs will be discussed including topical and IV NSAIDs. Evidence updates for acetaminophen effectiveness and decreased reliance on opioids means NSAIDs are back, baby!