This textbook presents mathematical models in bioinformatics and describes biological problems that inspire the computer science tools used to manage the enormous data sets involved. The first part of the book covers mathematical and computational methods, with practical applications presented in the second part. The mathematical presentation avoids unnecessary formalism, while remaining clear and precise. The book closes with a thorough bibliography, reaching from classic research results to very recent findings. This volume is suited for a senior undergraduate or graduate course on bioinformatics, with a strong focus on mathematical and computer science background.