The acne conglobata (AC)-, acne fulminans (AF)-, and isotretinoin-associated musculoskeletal syndromes are three distinct clinical entities. The AC-associated musculoskeletal syndrome occurs primarily in black men over the age of 22, who develop sacroilitis with or without a peripheral arthropathy. In contrast, the AF-associated musculoskeletal syndrome is found almost exclusively in white male teenagers. Fever, weight loss, and arthralgias are prominent components of this syndrome. A unique feature of the AF-associated musculoskeletal syndrome is osteolytic lesions that occur most frequently in the clavicle, sternum, long bones, and ilium. The isotretinoin-associated musculoskeletal syndrome occurs with equal frequency in male and female acne patients. Mild, transient myalgias and arthralgias are very common and do not require discontinuation of isotretinoin therapy. Asymptomatic, small, hyperostotic lesions of the spine occur in approximately 10% of acne patients with the isotretinoin-associated musculoskeletal syndrome.