Unique embryologic and immunologic aspects of the vulva contribute to the diagnostic and therapeutic challenges of managing vulvar problems. Individual variations in care of the genital region, defined by personal and societal “norms,” may at times exacerbate vulvar problems. Three dimensions are considered in the evaluation of a vulvar problem: 1) lesion type, 2) lesion location, and 3) associated systemic and laboratory findings. This review of vulvar disease highlights a number of common and problematic vulvar conditions. Treatment options for vulvar conditions are covered with an expanded discussion of newer immune response modifiers.