The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial has a total enrollment goal of almost 150,000 participants. These participants are being recruited at ten screening centers across the United States. All screening centers tested recruitment methodologies during a 1-year pilot phase. The main phase of recruitment was planned to take place over a 3-year period. The majority of participants are being recruited during the main phase of the study. Each of the screening centers tailors recruitment to its individual catchment area. Recruitment strategies in the PLCO trial are described. As the trial began, several protocol changes were made to help to increase enrollment. The National Cancer Institute (NCI) initiated recruitment efforts at the national level. The individual screening centers describe some of the specific recruitment experiences encountered. As the study progressed, the NCI implemented special initiatives to increase the enrollment of minority participants.