This book extends the original concept of the calcium paradox discovery, herein compiling more than 300 references in the field of calcium ion (Ca2+/cAMP) signalling pathways, neurotransmission and neurodegeneration, and neurological and psychiatric diseases. In this second edition, novel illustrations and tables (highlighting current medicines for treating these diseases, including their mechanism of action) offer improved insights into the concepts for students and clinicians. The description of other neurodegenerative diseases (Spinal muscular atrophy, Amyotrophic Lateral Sclerosis and Huntington´s disease) also adds further information with regards to treating these diseases. The growing increment in the life expectancy of the world’s population has increased concern about age-related neurological diseases (neurodegenerative diseases), such as Alzheimers (AD) and Parkinsons (PD) diseases, among others. It is now well-recognized that an imbalance of intracellular Ca2+ homeostasis contributes to the pathogenesis of neurological diseases like neurodegenerative diseases, including AD and PD, and others. Healthy brain aging can be promoted by regular exercise, moderation in caloric intake and engaging in intellectually challenging activities. These lifestyle factors may stabilize neuronal Ca2+ homeostasis. The discovery of the role of the calcium paradox due to the interaction between Ca2+ and cAMP signalling pathways (Ca2+/cAMP interaction) in neurotransmission, and neuroprotection, has subsidized the understanding of pathophysiology, and pharmacology, of the neurological and psychiatric diseases, opening a large pathway for the advancement of new pharmacological strategies for the treatment of these diseases. The proposal outlined in this book involves pharmaceuticals already approved, and may, in combination with improvements in lifestyle factors, allow sustained increments in the life quality of age-related neurological patients. Finally, this book briefly discusses other aspects of Ca2+/cAMP signalling pathways, such as their possible implications on cancer.