Small-animal imaging has a critical role in phenotyping, drug discovery and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo x-ray based small-animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.