This article focuses on methods based on fluctuation correlation spectroscopy to determine the formation of protein complexes in living cells. We present the principles of the fluctuation method applied to cells. We discuss the novelty and the promises of this approach. The emphasis is in the discussion of the underlying statistical assumptions of the image correlation spectroscopy analysis rather than in reviewing applications of the method. Although one example of the application of the fluctuation method is given, this article also contains simulations that are better suited to illustrate and support the basic assumptions of the method.