Aligning an acne diagnosis with a therapeutic strategy is the cornerstone of acne management. The challenges associated with treatment selection include the type and severity of the patient's acne as well as the mechanism of action of each medication and its ability to address one or more of the pathogenic factors of acne. Beyond the efficacy of treatment, the clinician must be able to address a number of factors that also will influence treatment success, the most important being compliance. The characteristics of treatment (e.g., tolerability profiles, dosing, vehicle) have a profound effect on compliance. In addition, patient characteristics, such as level of expectation, acne treatment knowledge, and willingness to be treated, impact a clinician's approach to management. First-line treatment sets the tone in the overall management of acne; thus, medication choice, patient education, and communication are critical to treatment success.