Transgenic animals – worms‎,‎ flies‎,‎ fishes‎,‎ rodents and livestock – are the invaluable models that have allowed the scientific and medical community to study in depth the mechanisms of gene and genome function and complex disease phenotypes‎,‎ to discover current and potential therapeutic approaches‎.‎ The first section of this book discusses advantages‎,‎ limitations‎,‎ pitfalls and applications of the powerful genome modification technologies such as Zinc‎-finger nucleases ‎(‎ZFNs‎)‎‎,‎ Transcription Activator‎-Like Effector Nucleases ‎(‎TALENs‎)‎‎,‎ CRISPR‎-Cas systems‎,‎ the Cre/loxP binary systems‎,‎ and lentiviral transduction‎,‎ which made possible to generate transgenic organisms in a more efficient way‎,‎ introduced a new era in gene function and cellular physiology analysis‎,‎ and opened new perspectives for biomedical research‎.‎ The optimized techniques such as somatic cell nuclear transfer and cytoplasmic injection of exogenous DNA into zygotes are also the promising tools to generate transgenic livestock with special traits‎.‎ A systematic overview on induced pluripotent stem cells ‎(‎iPSC‎)‎ generation and the applicative potential in the most important mammalian farm animal species is presented‎.‎ The remaining content of this book focuses on the animal models of Duchenne muscular dystrophy‎,‎ aging‎,‎ protein‎-misfolding diseases‎,‎ neurodegenerative diseases‎,‎ congenital diseases‎,‎ psychiatric disorders‎,‎ motor neuron disorders‎,‎ cancer‎,‎ immunodeficiency disease‎,‎ ribosomopathies‎,‎ and RASopathies among others‎.‎ The possible future directions and unresolved challenges are outlined‎.‎