Fresh fish and shellfish are highly perishable products due to their biological composition. Under normal refrigerated storage conditions, the shelf life of these products is limited by enzymatic and microbiological spoilage. However, with increasing consumer demands for fresh products with extended shelf life and increasing energy costs associated with freezing and frozen storage, the fish-processing industry is actively seeking alternative methods of shelf life preservation and marketability of fresh, refrigerated fish and at the same time economizing on energy costs. Additional methods that could fulfill these objectives include chemical decontamination, low-dose irradiation, ultra-high pressure, and modified atmosphere packaging (MAP). This review focuses on the biochemical and microbiological composition of fresh fish/shellfish, the spoilage patterns in these products, factors influencing spoilage, and the combination treatments that can be used in conjunction with refrigeration to extend the shelf life and keeping quality of fresh fish/shellfish. The safety concerns of minimally processed/MAP fish, specifically with respect to the growth of Clostridium botulinum type E, is also addressed.