Psoriasis is a chronic inflammatory skin disorder that is managed with systemic therapies for moderate to severe patients who fail first-line topical therapies and/or phototherapy. Dermatologists have many years of experience prescribing tumor necrosis factor-alpha (TNF-?) inhibitors, which are effective and are supported by a robust postmarketing safety record for psoriasis and other immune disorders. Physicians have also gained greater comfort prescribing the more recently approved interleukin-12/23 (IL-12/23) inhibitor Stelara (Janssen’s ustekinumab), which poses a threat to the dominance of the TNF-? inhibitors as the entrenched first-line therapies after conventional systemic agents. The treatment landscape for moderate to severe psoriasis is poised for significant expansion with the entry of emerging agents with novel mechanisms of action, most notably, the IL-17 inhibitors (i.e., Novartis’s secukinumab, Eli Lilly’s ixekizumab, Amgen’s brodalumab) and two agents with the advantage of oral administration (Pfizer’s Janus kinase inhibitor Xeljanz [tofacitinib] and Celgene’s phosphodiesterase-4 inhibitor Otezla [apremilast]). Additionally, with biosimilars on the horizon, the uptake of novel agents, some of which are expected to be priced at a premium to marketed therapies, will place greater strain on healthcare budgets, resulting in reimbursement restrictions. This report explores physician and payers attitudes toward the shifting treatment landscape for moderate to severe psoriasis.