Calves are born agammaglobulinemic and rely on colostrum consumption for the transfer of maternal passive immunity. Calves that fail to absorb adequate amounts of maternal antibodies from colostrum are commonly referred to as having failed transfer of passive immunity (FTPI). The overall aim of this dissertation was to explore the usefulness of FTPI testing in neonatal beef calves to predict their risk for subsequent illness or death. The objectives were to evaluate the impact of FTPI on pre-weaning disease in beef and dairy calves, quantify and compare the variance in IgG concentrations measured by radial immunodiffusion and serum total protein (STP) values measured by optical refractometry, and evaluate the correlation between herd-level prevalence of FTPI and herd-level prevalence of pre-weaning disease in beef calves. Evaluation of literature relevant to FTPI was compiled and assessed to quantify the impact of FTPI on pre-weaning disease in beef and dairy calves. A series of randomized trials were used to evaluate the variance in IgG concentrations and STP values from banked serum. Health records from multiple farms and IgG results were used to evaluate the relationship between FTPI and disease at the individual and herd-level. Failed transfer of passive immunity had a variable association with pre-weaning disease in beef and dairy calves. IgG concentrations were less precise than STP values especially when dilution was required. IgG concentrations and STP values were associated with an increased risk of disease in pre-weaned beef calves, but FTPI cut-off values poorly classified the risk for subsequent disease. The proportion of calves with FTPI was not correlated with the proportion of calves that developed pre-weaning disease. Using a single immunological factor, such as IgG concentration or STP, to predict disease results in the misclassification of disease risk and does not consider additional component causes of disease.