The Ca²⁺ signaling system seems to be ubiquitous in living organisms. It stands at crossroads of many signaling pathways and its study has brought many exciting facts about the stimulus response coupling in the cell. The Ca²⁺ concentration in the cytosol is regulated. The diverse problems associated with its study often require study of separate events in different cell compartments. This review briefly summarizes possible approaches to the study of Ca²⁺ signaling based on various physical principles and points out their advantages and also possible pitfalls. The approaches include electrochemical techniques, radiometric methods, bioluminescent and fluorescent indicators of Ca²⁺ and fluorescent proteins. The methods are not discussed comprehensively; the presented information should rather give a general insight into the topic.