Biological systems are highly complex systems, both spatially and temporally. They are rooted in an interdependent, redundant and pleiotropic interconnected dynamic network. The properties of a system are different from those of their parts, and they depend on the integrity of the whole. The systemic properties vanish when the system breaks down, while the properties of its components are maintained. The disease can be understood as a systemic functional alteration of the human body, which present with a varying severity, stability and durability. Biological systems are characterized by measurable complex rhythms, abnormal rhythms are associated with disease and may be involved in its pathogenesis, they are been termed "dynamic disease." Physicians have long time recognized that alterations of physiological rhythms are associated with disease. Measuring absolute values of clinical parameters yields highly significant, clinically useful information, however evaluating clinical parameters the variability provides additionally useful clinical information. The aim of this review was to study one of the most recent advances in the measurement and characterization of biological variability made possible by the development of mathematical models based on chaos theory and nonlinear dynamics, as approximate entropy, has provided us with greater ability to discern meaningful distinctions between biological signals from clinically distinct groups of patients.