In 2007, over 12-million people were diagnosed with cancer. According to the American Cancer Society, at least one third of these individuals are not expected to survive the disease, making cancer the second most prevalent cause of death worldwide. Systemic chemotherapy forms the mainstay of cancer treatment, and agents that disrupt mitotic spindle assembly - so called ;anti-mitotics' - are commonly used to treat a wide variety of cancers. Traditional anti-mitotic agents include the microtubule toxins such as taxol, other taxanes and the vinca alkaloids, all of which have proven successful in the clinic. However, patient response remains highly unpredictable, and drug resistance is common. In addition, toxicity is a problem. To address these limitations, a new generation of anti-mitotic drugs is being developed. As the first wave of these new agents enters clinical trails, much hope rests on their outcome. Meanwhile, significant attention is being focused on trying to predict which tumour types are likely to respond. In this Commentary, we outline recent advances in our understanding of how cancer cells respond to anti-mitotic drugs, and discuss the relevance of these studies to their use in the clinic.