•Biobetters are improved biological drugs, usually with better pharmacokinetics.•Biobetters can be considered in between biosimilars and innovative biological drugs.•Biobetters take about 10 years of development with investments of $500 millions.•Glycosylation and PEGylation are the most common strategies to develop biobetters.•Innovative trends of genetic engineering are promising for biobetters development. Biological drugs or biopharmaceuticals off patent open a large market for biosimilars and biobetters, follow-on biologics. Biobetters, in particular, are new drugs designed from existing ones with improved properties such as higher selectivity, stability, half-life and/or lower toxicity/immunogenicity. Glycosylation is one of the most used strategies to improve biological drugs, nonetheless bioconjugation is an additional alternative and refers to the covalent attachment of polymers to biological drugs. Extensive research on novel polymers is underway, nonetheless PEGylation is still the best alternative with the longest clinical track record. Innovative trends based on genetic engineering techniques such as fusion proteins and PASylation are also promising. In this review, all these alternatives wereexplored as well as current market trends, legislation and future perspectives.