A number of benign and malignant diseases with different causes, clinical features, management, and outcome can manifest as painful penile induration. The most common such conditions are active Peyronie disease, inflammation, trauma, venous or corporal thrombosis, acute ischemic disorders, and primary or secondary tumors. In patients with painful penile induration, a preliminary differential diagnosis is based on the patient's history and results of laboratory studies, penile inspection, and palpation. Imaging is often required to confirm the clinical diagnosis, assess the extent of disease, and determine patient treatment. A basic clinical investigation comprising penile inspection and palpation should be performed by the radiologist before imaging; such an evaluation is a great help in selecting the best imaging modality and examination technique. Moreover, acquisition of preliminary clinical information eases interpretation of the imaging features and facilitates identification of clinically relevant information that may result in a change in patient treatment. In standard clinical practice, color Doppler ultrasonography is often the first imaging modality used to evaluate patients with painful penile induration. This technique clearly demonstrates normal penile anatomy and its corresponding changes in most of the clinically relevant situations. Magnetic resonance imaging is the optimal imaging modality for tumor staging. Other imaging modalities are required less frequently.