Topological methods have been mostly used to study the action of enzymes and properties of naked DNA molecules. However topology can also be used to study chromosome organization. In this talk I will present three problems in which topology can be used to study complex organization of DNA. First I will present the problem of DNA knotting in bacteriophages. Understanding the organization of the genome in bacteriophages is important because bacteriophages are good models for DNA organization in some animal viruses (such as herpex viruses) and in DNA lipo-complexes used in gene therapy. Our approach is based on work by Liu, Calendar, Wang and colleagues that showed that DNA extracted from bacteriophage P4 is knotted. We have investigated these knots and shown that they are informative of the organization of the genome inside the capsid. I will present models that have been derived from these knots as well as the mathematical problems that this biological problem has generated. Second I will discuss the problem of chromosome intermingling of chromosome territories in the eukaryotic cell. During the G0/G1 phase of the cell cycle the eukaryotic genome is organized into chromosome territories. The positions of these territories as well as the structure along their surface are believed to play a major role in the formation of recurrent aberrations found in some genetic diseases and in some cancers. I will present some of our results on the topological implications of the Interchromosomal Network Model proposed by Branco and Pombo. In particular I will introduce our estimation of the linking probability of two neighboring chromosome territories assuming that chromatin fibers follow random trajectories. Third I will present some new and unpublished results on the linking of mitochondrial DNA in trypanosomes. Trypanosomatid parasites, trypanosoma and lishmania, are the cause of disease and death in many third world countries. One of the most unusual features of these organisms is the 3 dimensional organization of their mitochondrial DNA into maxi and minicircles. Minicircles are confined into a small volume and are interlocked forming a huge network. Some initial models for the organization of this network were proposed by Cozzarelli and Englund. Here we discuss some of the possible pathways for the formation and maintenance of this network as well as the mathematical results that derive from this problem. This work is in collaboration with: Y. Diao (UNC Charlotte), R. Scharein (SFSU), R. Kaplan (SFSU) and M. Vazquez (SFSU).