This chapter discusses some of the most common complaints that results in the client’s visit to the primary care provider–infection. As always, effective management plans can only be developed once the provider has identified the correct source of the infection and corresponding pathology. Clients presenting with complaints of infection often begin by visiting the primary care provider. The chapter describes the hot topics in infectious disease that the primary/urgent care nurse practitioner is expected to diagnose or perhaps initiate management of. The hot topics include Lyme disease, travel medicine, methicillin-resistant Staphylococcus aureus, adult immunization schedule, antimicrobial stewardship, and Clostridium difficile.