Adrenal lesions are routinely encountered incidentally in clinical practice. Although most of these lesions are benign, malignancy needs to be excluded. Therefore, the initial clinical workup is to exclude aggressive characteristics suggesting malignancy and to identify characteristics predictive of the most common benign lesion, an adrenal adenoma. Predicting a benign adenoma using a variety of imaging modalities has been widely studied using unenhanced computed tomography (CT), contrast enhanced CT, and magnetic resonance (MR) imaging. This review article describes the currently used imaging protocols and clinical interpretation criteria of common adrenal lesions. An adenoma can be predicted if a homogenous soft tissue adrenal mass demonstrates low attenuation (upper threshold value of 10 Hounsfield Units) on unenhanced CT, demonstrates an absolute enhancement washout of ≥ 60% and/or relative enhancement washout of ≥ 40% on adrenal washout contrast enhanced CT, or demonstrates signal loss in opposed-phased MR imaging. If an adrenal adenoma cannot be predicted based upon these criteria, the lesion should be evaluated for other imaging characteristics that suggest a specific pathology, such as an adrenal cyst or myelolipoma. Although nonspecific and with limitations, 18F-fluorodeoxyglucose (FDG) PET/CT has a potential role for differentiating benign from malignant lesions based upon the amount of radiopharmaceutical uptake with malignant lesions generally having greater uptake. If clinical and/or hormonal screening suggests a pheochromocytoma, consideration can be given to 18F-dihydroxyphenylalanine (DOPA) or 123I-metaiodobenzylguanidine (MIBG) in addition to CT and MR. Finally, this review proposes a diagnostic work-up strategy for routine use in clinical practice.