Evaluating various algorithms for the inter-subject registration of brain magnetic resonance images (MRI) is a necessary topic receiving growing attention. Existing studies evaluated image registration algorithms in specific tasks or using specific databases (e.g., only for skull-stripped images, only for single-site images, etc.). Consequently, the choice of registration algorithms seems task- and usage/parameter-dependent. Nevertheless, recent large-scale, often multi-institutional imaging-related studies create the need and raise the question whether some registration algorithms can 1) generally apply to various tasks/databases posing various challenges; 2) perform consistently well, and while doing so, 3) require minimal or ideally no parameter tuning. In seeking answers to this question, we evaluated 12 general-purpose registration algorithms, for their generality, accuracy and robustness. We fixed their parameters at values suggested by algorithm developers as reported in the literature. We tested them in 7 databases/tasks, which present one or more of 4 commonly-encountered challenges: 1) inter-subject anatomical variability in skull-stripped images; 2) intensity homogeneity, noise and large structural differences in raw images; 3) imaging protocol and field-of-view (FOV) differences in multi-site data; and 4) missing correspondences in pathology-bearing images. Totally 7,562 registrations were performed. Registration accuracies were measured by (multi-)expert-annotated landmarks or regions of interest (ROIs). To ensure reproducibility, we used public software tools, public databases (whenever possible), and we fully disclose the parameter settings. We show evaluation results, and discuss the performances in light of algorithms’ similarity metrics, transformation models and optimization strategies. We also discuss future directions for the algorithm development and evaluations.