Estimation of appropriate sample size for prevalence surveys presents many challenges, particularly when the condition is very rare or has a tendency for geographical clustering. Sample size estimate for prevalence studies is a function of expected prevalence and precision for a given level of confidence expressed by the z statistic. Choice of the appropriate values for these variables is sometimes not straight-forward. Certain other situations do not fulfil the assumptions made in the conventional equation and present a special challenge. These situations include, but are not limited to, smaller population size in relation to sample size, sampling technique or missing data. This paper discusses practical issues in sample size estimation for prevalence studies with an objective to help clinicians and healthcare researchers make more informed decisions whether reviewing or conducting such a study.