Salmonellosis is associated with massive public health and economic losses globally. It is estimated to cost poultry farmers in the United States of America up to US$114 million annually. Attempts to develop effective vaccines and eradicate Salmonella enterica serovar Enteritidis (S. Enteritidis) from hen houses are undermined by serious limitations. This article reviews documented contamination routes and limitations to the rapid development of vaccines. Host-parasite interactions and clinical pathology are discussed and methods for reducing S. Enteritidis infection and transmission suggested.