Introduction: Current acne treatment guidelines, as well as, treatment efficacy, safety, tolerability and patient preferences must all be considered in determining appropriate treatment regimes. Literature can assist physicians' evidence-based recommendations according to these factors. Areas covered: To determine the current and future direction of pharmacotherapy for treatment of acne, a PubMed search was conducted to identify all clinical trials involving the treatment of acne from 2009 to 2012. A total of 65 publications met inclusion criteria and were reviewed. Literature was heavily focused on the efficacy and tolerability of topical combination therapies and supported their use compared with monotherapy. A few studies on topical antiandrogens and antioxidants showed an alternative approach to targeting acne. Studies on oral monotherapy provided some evidence for the use of pulsed azithromycin for acne in adolescents. Literature also supports the use of low-dose isotretinoin for moderate acne, which was comparable in efficacy to high-dose regimes and better tolerated. Expert opinion: Combination acne therapy, whether it be combination topical therapy or combination oral and topical therapy, is well supported by recent studies. Given the multifactorial pathogenesis of acne and the hurdles of adherence to treatment, we anticipate greater development of and reliance on combination acne products in the future.