Cellulite is the unsightly dimpling and nodularity frequently found on the thighs and buttocks of post-adolescent women. The anatomy and pathophysiology of this unwanted condition is poorly understood. The paucity of research studies to date has led to a dormancy of scientifically based therapeutic options that are effective and tolerable. The purpose of this study is to evaluate the tolerability and efficacy of a novel topical agent based on a plausible pathophysiologic mechanism in the treatment of cellulite, and to compare the efficacy of this agent used in combination with an occlusive bioceramic-coated neoprene garment, to the agent used alone without occlusion. We will also review the current understanding of the etiology and nature of cellulite and summarize available treatment options. Twenty women with a moderate degree of cellulite were entered into a four-week, double-blinded, randomized trial where an anti-cellulite cream was applied to the affected sites on a nightly basis. Each subject was randomized to receive occlusion by a bioceramic-coated neoprene garment on either the right or left leg, with the contralateral side serving as a control with no occlusion. High-quality digital photography was taken before treatment and after four weeks at various angles, with tangential full-spectrum lighting. Four blinded, independent dermatologist reviewers assessed the photographs for improvement. Subjects completed questionnaire forms to assess tolerability and efficacy. Of the 17 subjects who completed the study, 76% noticed an overall improvement in their cellulite, with 54% reporting greater improvement in the thigh that received garment occlusion. The average measured decrease in thigh circumference was 1.2 cm, noting a 1.3 cm reduction with occlusion and a 1.1 cm reduction without occlusion. Upon review of the pre- and post-study photographs, the dermatologist evaluators found an improvement in 65% of treated legs with occlusion, and 59% of treated legs without occlusion. Further, the evaluators found the occluded thighs to show greater improvement than the non-occluded thighs in 65% of subjects. The topical agent used in this study was found to be effective in reducing the appearance of cellulite. Bioceramic-coated neoprene garment occlusion potentiates the effect of this topical agent in cellulite reduction. The success of this study validates the pathophysiologic mechanism used to formulate the topical agent used.