Product validation and reliability demonstration require testing of limited samples and probabilistic analyses of the test data. The uncertainties introduced from the tests with limited sample sizes and the assumptions made about the underlying probabilistic distribution will significantly impact the results and the results interpretation. Therefore, understanding the nature of these uncertainties is critical to test method development, uncertainty reduction, data interpretation, and the effectiveness of the validation and reliability demonstration procedures. In this paper, these uncertainties are investigated with the focuses on the following two aspects: (1) fundamentals of the RxxCyy criterion used in both the life testing and the binomial testing methods, (2) issues and benefits of using the two-parameter Weibull probabilistic distribution function. Finally, the potential impact of this research on product validation and reliability demonstration are indicated and some recommendations are provided.