The emergence of data from clinical trials of biologics, the approval of new biologics, and our improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for the treatment of moderate-to-severe psoriasis . Biologics currently approved for the treatment of psoriasis include tumor necrosis factor inhibitors, interleukin (IL) -17 inhibitors, ustekinumab (an IL-12/23 inhibitor), and IL-23 inhibitors . Data from clinical trials and studies of the safety and efficacy of biologics provide essential information for the personalization of patient care . We discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment recommendations according to current evidence, and propose psoriasis treatment algorithms . Our discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer, lymphoma, and latent tuberculosis . We make evidence-based treatment recommendations for special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and pregnant and breastfeeding patients with psoriasis . Ultimately, individualized recommendations that consider patient preferences, disease severity, comorbid conditions, and additional risk factors should be offered to patients and updated as new trial data emerges.