Longitudinal studies offer significant advantages in rendering data commensurate with the complexity of human development. However, incomplete enrolment and attrition over time can introduce bias. Furthermore, there is a scarcity of evaluative information on cohorts in developing countries. This paper documents various strategies adopted to minimize loss to follow up and describes a retrospective analysis of a small group of families who were missed during initial enrolment and through several subsequent rounds of data collection of the Birth to Twenty (BT20) birth cohort in Soweto-Johannesburg, South Africa that began in 1990. A purposive case study approach was used, and 10 of the 119 families missed at enrolment were interviewed to investigate why these families were not enrolled into the study. The findings demonstrate that high mobility, both within urban areas and between urban and rural areas, are a major challenge for longitudinal studies in densely populated urban areas. In addition, enrolment was also affected by individuals changing their names, largely motivated to facilitate access to employment under Apartheid, as well as varying motivations for participating in research. Longitudinal studies in the developing country context must be mindful of the political, social and economic climate that influences enrolment and ongoing cohort maintenance.