Anelloviruses are small, circular single-stranded DNA viruses infecting vertebrates, including humans. They are remarkably omnipresent, probably infecting the entire human population. Anelloviruses have been detected in a large variety of human tissues, and are known to be a dominating virus family in human blood. Besides the omnipresence, anelloviruses are also extremely genetically diverse. So far, the anellovirus infection has not been linked to any disease, which may have caused the fact that even though these viruses are known to science for almost 30 years, they are largely understudied. In this thesis, a number of fundamental knowledge gaps are addressed: early-life infection (colonization), transmission, nature of infection (chronic or acute), dynamics, evolution and anellovirus-host interactions. The availability of next-generation sequencing techniques and longitudinally collected clinical samples allowed us to perform novel and comprehensive studies on the topics. In Chapter 2 we explore the early-life colonization using a large set of blood samples from children and breast milk samples. Mother-to-child transmission of anelloviruses is explored in Chapter 3, in which we sequenced anellovirus blood viromes (anellomes) of five mother and child pairs. In Chapter 4, we studied the dynamics of anellome of two subjects followed-up for more than 30 years. We took a closer look at the same dataset in Chapters 5 and 6, in which we respectively explored anellovirus evolution and the role of innate immunity in restriction of anelloviruses.