['A hierarchy, characterized by tree-like relationships, is a natural method of organizing data in various domains. When considering an unsupervised machine learning routine, such as clustering, a bottom-up hierarchical (BU, agglomerative) algorithm is used as a default and is often the only method applied.', 'We show that hierarchical clustering that involve global considerations, such as top-down (TD, divisive), or glocal (global-local) algorithms are better suited to reveal meaningful patterns in the data. This is demonstrated, by testing the correspondence between the results of several algorithms (TD, glocal and BU) and the correct annotations provided by experts. The correspondence was tested in multiple domains including gene expression experiments, stock trade records and functional protein families. The performance of each of the algorithms is evaluated by statistical criteria that are assigned to clusters (nodes of the hierarchy tree) based on expert-labeled data. Whereas TD algorithms perform better on global patterns, BU algorithms perform well and are advantageous when finer granularity of the data is sought. In addition, a novel TD algorithm that is based on genuine density of the data points is presented and is shown to outperform other divisive and agglomerative methods. Application of the algorithm to more than 500 protein sequences belonging to ion-channels illustrates the potential of the method for inferring overlooked functional annotations. ClustTree, a graphical Matlab toolbox for applying various hierarchical clustering algorithms and testing their quality is made available.'] Do global considerations in hierarchical clustering reveal meaningful patterns in data?