Exact solutions of nonlinear differential equations are of great importance to the theory and practice of complex systems. The main point of this review article is to discuss a specific methodology for obtaining such exact solutions. The methodology is called the SEsM, or the Simple Equations Method. The article begins with a short overview of the literature connected to the methodology for obtaining exact solutions of nonlinear differential equations. This overview includes research on nonlinear waves, research on the methodology of the Inverse Scattering Transform method, and the method of Hirota, as well as some of the nonlinear equations studied by these methods. The overview continues with articles devoted to the phenomena described by the exact solutions of the nonlinear differential equations and articles about mathematical results connected to the methodology for obtaining such exact solutions. Several articles devoted to the numerical study of nonlinear waves are mentioned. Then, the approach to the SEsM is described starting from the Hopf-Cole transformation, the research of Kudryashov on the Method of the Simplest Equation, the approach to the Modified Method of the Simplest Equation, and the development of this methodology towards the SEsM. The description of the algorithm of the SEsM begins with the transformations that convert the nonlinearity of the solved complicated equation into a treatable kind of nonlinearity. Next, we discuss the use of composite functions in the steps of the algorithms. Special attention is given to the role of the simple equation in the SEsM. The connection of the methodology with other methods for obtaining exact multisoliton solutions of nonlinear differential equations is discussed. These methods are the Inverse Scattering Transform method and the Hirota method. Numerous examples of the application of the SEsM for obtaining exact solutions of nonlinear differential equations are demonstrated. One of the examples is connected to the exact solution of an equation that occurs in the SIR model of epidemic spreading. The solution of this equation can be used for modeling epidemic waves, for example, COVID-19 epidemic waves. Other examples of the application of the SEsM methodology are connected to the use of the differential equation of Bernoulli and Riccati as simple equations for obtaining exact solutions of more complicated nonlinear differential equations. The SEsM leads to a definition of a specific special function through a simple equation containing polynomial nonlinearities. The special function contains specific cases of numerous well-known functions such as the trigonometric and hyperbolic functions and the elliptic functions of Jacobi, Weierstrass, etc. Among the examples are the solutions of the differential equations of Fisher, equation of Burgers-Huxley, generalized equation of Camassa-Holm, generalized equation of Swift-Hohenberg, generalized Rayleigh equation, etc. Finally, we discuss the connection between the SEsM and the other methods for obtaining exact solutions of nonintegrable nonlinear differential equations. We present a conjecture about the relationship of the SEsM with these methods.