Selection of a therapy for a patient with alopecia areata (AA) is frequently based on the age of the patient, disease extent, perhaps disease duration, patient expectations, cost of therapy in terms of time commitment, and financial resources, as well as the results of screening laboratory studies that rule out the presence of other co-morbidities such as anemia, low iron stores, thyroid abnormalities, low vitamin D, or other autoimmune diseases. Although there is currently no cure for AA and no universally proven therapy that induces and sustains remission, many therapies are available which can be of benefit to both affected children and adults. Before selecting a treatment for patients with extensive long-standing AA, a scalp biopsy may provide useful information about the degree of inflammation and follicle differentiation. Recent clinical and translational research observations with the systemic Janus kinase (JAK) inhibitors and interleukin-2 (IL-2) have excited the clinical and AA patient communities and have led to clinical trials, as well as to the off-label use of these more expensive and targeted systemic therapies.