A handbook is a type of reference work, or other collection of instructions, that is intended to provide ready reference. A vade mecum (Latin, "go with me") or pocket reference is intended to be carried at all times.
Handbooks may deal with any topic, and are generally compendiums of information in a particular field or about a particular technique. They are designed to be easily consulted and provide quick answers in a certain area. For example, the MLA Handbook for Writers of Research Papers is a reference for how to cite works in MLA style, among other things.
"Handbook" is sometimes applied to documents that are produced within an organization that are not designed for publication -- such as a company handbook for HR, for instance. In this case, the term is used nearly synonymously with "manual."