Hormones have been observed to initiate tumors in animals and are thought to be involved in cellular selection and/or progression of neoplastic lesions in humans. Hormones are the ‘First messengers’ in mammalian systems as they allow cell to cell and organ to organ communication A ‘second messenger’ system is currently being elucidated. This second messenger system involves several cellular membraneous and intracellular components which act to relay extracellular messages to intracellular targets including the genomic machinery within the nucleus. The current manuscript reviews and discusses the following components of the second messenger system in normal versus neoplastic tissues: hormone binding, message transduction, adenylate cyclases, guanylate cyclases, cyclic AMP, cyclic GMP, cyclic nucleotide phosphodiesterases, cyclic nucleotide binding proteins, protein kinases (protein phosphorylation), and phosphoprotein dephosphatases (phosphoprotein de-phosphorylation).