The incidence of renal cell carcinoma is increasing globally. Targeted agents offer treatment options that were not available less than a decade ago. However, it is important to carefully select therapy for each individual patient, weighing both the drug efficacy and tolerability profile and patient-related factors, such as adherence, age and comorbidities. Based on our clinical experience in treating patients with renal cell carcinoma, this article offers our opinions on factors that characterize patients for whom sorafenib may serve as a viable first-line therapeutic option.