A look into fractional calculus and its applications from the signal processing point of view is done in this paper. A coherent approach to the fractional derivative is presented, leading to notions that are not only compatible with the classic but also constitute a true generalization. This means that the classic are recovered when the fractional domain is left. This happens in particular with the impulse response and transfer function. An interesting feature of the systems is the causality that the fractional derivative imposes. The main properties of the derivatives and their representations are presented. A brief and general study of the fractional linear systems is done, by showing how to compute the impulse, step and frequency responses, how to test the stability and how to insert the initial conditions. The practical realization problem is focussed and it is shown how to perform the input-ouput computations. Some biomedical applications are described. (C) 2010 Elsevier B.V. All rights reserved.