To provide successful care for psoriasis patients, treatments must be efficacious and safe as well as improve the patients' overall well-being. Efficacy and safety are generally established by randomized, controlled clinical trials. However, because of the rigid conditions under which randomized, controlled clinical trials are conducted, they do not reflect patient experience in real-life clinical practice; that is, they do not measure treatment effectiveness in the real world. Factors such as adherence to therapy, treatment satisfaction, and quality of life may be rated unrealistically high in randomized, controlled clinical trials. Observational studies using real-life patient populations, and capturing patient-reported outcomes, are useful at better assessing a treatment's effectiveness. Healthcare professionals and payers may gain valuable insights from patient-reported outcomes data that can be used in making treatment decisions. For localized plaque psoriasis, topical vitamin D analog and corticosteroid combination therapy is recommended as a first-line treatment. This commentary addresses the concept of clinical trial efficacy versus real-life effectiveness in psoriasis treatment using vitamin D and corticosteroid topical combination therapy as a model.