Integer linear programming (ILP) is a versatile modeling and optimization technique that is increasingly used in non-traditional ways in biology, with the potential to transform biological computation. However, few biologists know about it. This how-to and why-do text introduces ILP through the lens of computational and systems biology. It uses in-depth examples from genomics, phylogenetics, RNA, protein folding, network analysis, cancer, ecology, co-evolution, DNA sequencing, sequence analysis, pedigree and sibling inference, haplotyping, and more, to establish the power of ILP. This book aims to teach the logic of modeling and solving problems with ILP, and to teach the practical 'work flow' involved in using ILP in biology. Written for a wide audience, with no biological or computational prerequisites, this book is appropriate for entry-level and advanced courses aimed at biological and computational students, and as a source for specialists. Numerous exercises and accompanying software (in Python and Perl) demonstrate the concepts.