Owing to their interesting physical and chemical properties, carbon nanotubes (CNTs) have attracted wide attentions in nanomedicine for applications in biological sensing, drug delivery, as well as biomedical imaging. The in vivo behaviors and toxicology of CNTs in biological systems, which are important fundamental questions, although have been intensively studied in recent years, remain to be clarified as distinctive results have been reported by various teams, confusing the scientific community as well as the public. In this article, we review the research on the in vivo behaviors of CNTs, and summarize the toxicity studies of CNTs in animals by different groups. Similar to other nanomaterials, the in vivo pharmacokinetics and biodistribution of CNTs are closely associated with their surface coatings. The excretion of CNTs from animals may happen via renal and fecal pathways, depending on the CNT surface chemistry, shape, and sizes. Regarding the toxicology of CNTs, which has been a debating topic for years, the administration routes, doses, and again the surface functionalization are critical to the in vivo toxicity of nanotubes. Much more efforts are still required to develop functional CNT bioconjugates with improved biocompatible coatings and controllable optimal sizes to achieve fast excretion and minimal toxicity, for various applications in biomedicine.