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Image spam is a type of e-mail spam that embeds spam text content into graphical images to bypass traditional text-based e-mail spam filters. To effectively detect image spam, it is desirable to leverage image content analysis technologies. However, most previous works of image spam detection focus on filtering the image spam on the client side. We propose a more desirable comprehensive solution which embraces both server-side filtering and client-side detection to effectively mitigate image spam. On the server side, we present a nonnegative sparsity induced similarity measure for cluster analysis of spam images to filter the attack activities of spammers and fast trace back the spam sources. On the client side, we employ the principle of active learning where the learner guides the users to label as few images as possible while maximizing the classification accuracy. The server-side filtering identifies large image clusters as suspicious spam sources and further analysis can be performed to identify the real sources and block them from the beginning. For those spam images which survived the server-side filter, our active learner on the client side will further guide the users to interactively and efficiently filter them out. Our experiments on an image spam data-set collected from the e-mail server of our department demonstrate the efficacy of the proposed comprehensive solution.