Lab-on-a-chip (LOC) devices are broadly used for research in the life sciences and diagnostics and represent a very fast moving field. LOC devices are designed, prototyped and assembled using numerous strategies and materials but some fundamental trends are that these devices typically need to be (1) sealed, (2) supplied with liquids, reagents and samples, and (3) often interconnected with electrical or microelectronic components. In general, closing and connecting to the outside world these miniature labs remain a challenge irrespectively of the type of application pursued. Here, we review methods for sealing and connecting LOC devices using standard approaches as well as recent state-of-the-art methods. This review provides easy-to-understand examples and targets the microtechnology/engineering community as well as researchers in the life sciences.