In this chapter, large-scale DNA rearrangements, including deletions, amplifications, and other DNA alterations such as interchromosomal interactions, are dealt with and special attention is given to the instability of Streptomyces species. Streptomyces species belong to the order Actinomycetales and are filamentous gram-positive bacteria living in the soil. They possess a complex life cycle that begins on solid medium by the germination of spores to form the vegetative mycelium. The phenotypic instability is closely associated with genomic rearrangements, such as large deletions and intense tandem DNA amplifications. The linear structure of the chromosomal DNA raises questions about the replication mechanisms, the unstable region corresponding to natural termini of chromosomal replication. An interesting characteristic of genetic instability is that it is inducible. Hypotheses about the possible origin of this instability are based on reports of studies where the level of instability has been altered by a variety of treatments. The spontaneous frequencies of instability can be increased by treatments as varied as exposure to UV light, culture in the presence of intercalating agents, cold storage, temperature shifts during culture, nutritional shifts, and the regeneration of protoplasts. Homologous recombination is involved in numerous cases of chromosome rearrangement in bacteria. Genes may be directly identified by the phenotype accompanying their deletion or amplification. The exchanges of the terminal regions could be due to the structure which is suspected to keep the DNA ends together in vivo.