The MARCH-INSIDE approach is a computational method that can be used to seek Quantitative Structure-Property Relationships (QSAR) models in genes and their product RNA and/or proteins without to rely upon sequence alignment. The present chapter is devoted to review previous applications of MARCH-INSIDE predict the function of new sequences experimentally discovered and discuss the legal issues related to using QSAR and in general Bioinformatics models in real research and development problems in Plant Genomics. In this sense, first we give some details on the theoretical basis of MARCH-INSIDE. Next, we review the previous works reported on the applications of MARCH-INSIDE in Plant Genomics including the isolation and prediction of new gene and/or gene products (protein, RNAs) such as: 1) Ribonucleases (RNAses), 2) 1-aminocyclopropane-1-carboxylate oxidases and synthases (ACOs), 3) Polygalacturonases (PGs) and 4) 18S Ribosomal RNAs (18S-rRNAs). Last, we discuss the legal issues that should be considered when use MARCH-INSIDE or other QSAR approaches such as: copyright, patents, and taxes. From this chapter it is possible to conclude that MARCH-INSIDE models may be applied in Plant Genomics and Biotechnology to find new interesting enzymes without relying upon alignment techniques. The classification power of these models is comparable to sequence-alignment based methods like BLAST. There are legal aspects derived from the use of QSAR models in this field that should be strongly taken into consideration when we use it.