Clustering is the task of organizing a set of objects into meaningful groups. These groups can be disjoint, overlapping, or organized in some hierarchical fashion. The key element of clustering is the notion that the discovered groups are meaningful. This definition is intentionally vague, as what constitutes meaningful is to a large extent, application dependent. In some applications this maytranslate to groups in which the pairwise similarity between their objects is maximized, and the pairwise similarity between objects of different groups is minimized. In some other applications this may translate to groups that contain objects that share some keycharacteristics, even though their overall similarity is not the highest. Clustering is an exploratory tool for analyzing large datasets, and has been used extensively in numerous application areas.The primary goal of this chapter is to provide an overview of the various issues involved in clustering large datasets, describe the merits and underlying assumptions of some of the commonly used clustering approaches, and provide insights on how to cluster datasets arising in various areas within life-sciences.