This paper presents an overview of the important logistical and methodological considerations when conducting research in this setting. This paper is written for researchers new to the general practice setting. We discuss logistical challenges such as literature searching, ethical considerations, recruitment and retention of GPs, practices and patients, working with practices, and financial considerations. Methodological considerations including issues relating to patient recruitment, clustering, Hawthorne effect, ensuring conformity of intervention, avoiding contamination, and confounders are also discussed. A checklist for researchers contemplating research in this setting is supplied.