Telomeres contain ~1/3000th the DNA in a human cell, yet shelter us from oncogenic progression, monitor the number of cell divisions and respond to toxic insult from agents producing DNA damage. This is accomplished via pathways which signal the presence of DNA lesions. A central feature of the telomere is its 3-dimensional structure. In 1999 we showed that the ends of mammalian telomeres loop back and invade the preceding telomeric DNA. T-loops have now been found from humans to yeast (with genetic manipulation). Recently Doksani in the de Lange and Zhang labs used STORM light microscope imaging to confirm the presence of t-loops in mouse cells and observed loop frequencies and dimensions similar to what we observed by EM. Telomeres are rich in complex structural elements including the t-loop, t-loop junction (more complex than previously believed), and R-loops. The latter are a recently recognized component of telomeres. R-loops can lead to genomic instability, gross chromosomal rearrangements, and cancer. R-loops may represent one of the greatest threats to telomeres yet may be needed to form protective t-loops. Our current work is focused on understanding more about the role of R-loops at the telomere using a variety of structural and biochemical tools including electron microscopy