Acute scrotal pain has a broad differential diagnosis, including infections of the testes and associated anatomical structures. Epididymitis is a common cause of acute scrotal pain typically caused by sexually transmitted bacterial pathogens. Clinical signs and symptoms that support the diagnosis include pain, swelling, and induration of the epididymis. There may be associated dysuria. When epididymitis is suspected, diagnostic testing for gonorrhea and chlamydia infection should be performed and empiric antibiotic treatment initiated while awaiting the results. Orchitis, or inflammation of one or both testicles, is uncommon in the absence of epididymitis and urethritis since the infections, when caused by bacterial pathogens, occur as pathogens migrate, in retrograde fashion, from the urethra to the scrotal structures. Orchitis can also develop secondary to an acute viral infection. In these circumstances, the testes (usually both) are infected during a period of viremia. The testicular inflammation often occurs in the absence of epididymitis since the testes are infected via the hematogenous route rather than by retrograde migration of the pathogen through the genitourinary tract. Mumps virus remains the most common cause of acute viral orchitis, although several other viruses are also known to cause acute testicular pain and swelling, including SARS-CoV-2. The clinical presentation of acute bacterial prostatitis includes dysuria, urinary frequency, and genital or lower back pain. Fever and chills are also common. When acute prostatitis and epididymitis are seen together, gonorrhea and chlamydia are the likely culprits. When the infection is localized to the prostate, other bacterial agents need to be considered as well. Acute bacterial prostatitis is more common among males who have sex with males and as a complication of a recent urinary tract infection or urologic procedure.