Clinical research performed in family physicians' offices is critical for building an expanded knowledge base for modern health care. Practitioners do not usually have the time, funds, or research expertise to conduct clinical studies. Organized networks can accomplish this goal. Large-area networks, composed of many separate practice sites from a wide geographic area, are valuable sources of information for describing the natural history of disease. These observational studies usually consist of data collection during clinical practice. Experimental trials include evaluations of new protocols, diagnostic tests, or therapies, often in a randomized and blinded fashion. Because of the difficulties in adhering to a standardized protocol, experimental trials are rarely undertaken in the busy clinician's office. Similarly, it may be difficult to standardize these studies in large-area networks. Smaller networks, often in a single community, can feasibly perform more complex studies. Important strategies are required to avoid loss of interest, lack of continuity, and conflict of interest.