Calcium is an essential intracellular messenger that plays a vital role in controlling a broad range of cellular processes, including apoptosis. This review offers an in-depth analysis of calcium’s multifaceted role in apoptosis regulation, focusing on the associated signaling pathways and molecular mechanisms. We will explore calcium’s impact on apoptosis through its effects on different cellular compartments, such as the mitochondria and endoplasmic reticulum (ER), and discuss the connection between calcium homeostasis and ER stress. Additionally, we will highlight the interplay between calcium and various proteins, including calpains, calmodulin, and Bcl-2 family members, and the role of calcium in regulating caspase activation and pro-apoptotic factor release. By investigating the complex relationship between calcium and apoptosis, this review aims to deepen our comprehension of the fundamental processes, and pinpointing possible treatment options for illnesses associated with imbalanced cell death is crucial.