The limited supply of beef cattle is one of the greatest challenges facing the beef industry globally and is a factor reflected in the annual decline in fed cattle harvest. Calf-fed Holsteins (CFH) represent an opportunity to fill the void in beef cattle supply; however, because of the differences that exist compared with beef cattle, a science based approach is required to optimize production and profitability. The CFH often is overlooked in academic research. The research based on dairy heifer calves or beef cattle is often extrapolated to CFH. The objective of this presentation is to discuss the implications of Neonatal Nutrition Programs (NNP) on health and lifetime performance in CFH. The success of NNP (birth to <205 kg) should take into consideration the environment, genetics, immune status, and inherent variation that exist in CFH populations. During NNP, the greatest contributor to the feed-only cost of gain is the milk feeding program. More research is required to optimize growth and production goals without compromising the well-being of the calf. Understanding how NNP affects the immune status/response of the calf and implications on lifetime health and growth is pivotal. Nutrigenomics is an avenue of research that could expand the understanding of how clinical or subclinical disease change nutrient requirements and potentially allowing for development of mitigation strategies. Another area of research required in the CFH encompasses determining the effects of lifetime feeding of CFH through understanding the potential interactions between NNP at the calf ranch and the eventual feeding program at the feedlot. Research regarding grain type, grain processing, by-product use, protein sources and concentrations, and roughage level at the calf ranch is critical. Understanding the biology of the CFH across all growth stages is needed so that economic models can be developed. Understanding the economic contribution of different aspects of biology allows for sensitivity determination of key economic variables that should help identify research priorities. A multidisciplinary research approach to understanding the CFH is required to meet the increasing demand for animal protein without compromising the overall well-being and sustainability of this industry.