Timely and appropriate nutritional interventions for patients with cancer and/or human immunodeficiency virus (HIV) infection require adoption of routine nutritional screening and comprehensive evaluations into clinical practice. Traditionally, the clinical skills necessary for comprehensive nutritional evaluation have not been a part of medical education. Likewise, the importance of nutritional screening and assessment has not been fully appreciated. In the context of current health care, these skills are increasingly important in maintaining or improving patient care and improving clinical and economic outcomes. It is imperative that nutritional screening be routinely implemented in all clinical settings (eg, office practices, clinics, preadmission units, homecare) to offset the impact of decreased rates of hospital admission. Hospitals have traditionally been the setting for dietetic screening and intervention and nutritional support services. Therapy for patients with cancer or HIV infection is increasingly being managed primarily or entirely in an outpatient setting. When nutritional risk or deficit is identified on screening, it is important to carry out sequential reassessment after intervention. This article reviews the principles of nutritional screening and comprehensive assessment. It includes a detailed overview of an instrument that can be used for either nutritional screening or assessment in patients with either malignancy or HIV infection.