Two important types of models for reliability and genetics, the semi-Markov and hidden semi-Markov models are presented in this book. Their importance relies on the fact that they generalize several previous models and provide new possibilities to handle real problems. For reliability scientists and engineers, this book comes with a new method for studying systems reliability and it offers modelling and estimation tools. As for the biologists, this work offers them a more adapted model for DNA analysis, namely the hidden semi-Markov model, which is more flexible than the hidden Markov models, extensively used in this field. Moreover, the hidden semi-Markov framework can be used in many other applications, such as reliability, signal treatment, speech or image processing, among others.