Secretory proteins that are involved in modulating hosts are called as effectors. Lately, finding these important proteins from a large array of other gene products have been a focus area in many high funding research programs. However, since the biological data is accumulating at a much faster rate now than ever before, this search process can be compared to finding a needle in the haystack. Conventional laboratory-based methods require critical experiments, extended time and high cost which in many cases result in failure of testing hypothesis. Using high throughput sequencing technologies, whole genome sequences are generated much more quickly and efficiently. The avalanche of genomics data has ushered new opportunities into discovery of large number of novel extra cellular secretory proteins that usually lie undetected with conventional methods. Recently powerful bioinformatics methods have emerged that can predict effectors from whole genome data of pathogens, commensal, symbiotic and environmental microorganisms much easily. In this review, we present a broad overview of these biological molecules that modulates host response in different ways in many organisms-pathogenic, non-pathogenic and commensal. We also catalogue the motifs associated with many secretory mechanisms and their prediction algorithms.