High-throughput single-cell RNA sequencing has transformed our understanding of complex cell populations, but cannot measure single cell phenotypic information provided by protein levels. We recently described cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), a method in which oligonucleotide-labeled antibodies are used to integrate cellular protein and transcriptome measurements into an efficient, single-cell readout. Individual antibodies are labeled with oligos with different sequence barcodes, enabling the number of individual markers that can be measured simultaneously to far surpass what can be measured by cytometry-based approaches, while also measuring the transcriptome. CITE-seq is compatible with existing single-cell sequencing approaches and will readily scale as the throughput of these methods increase. A technically related approach, Cell Hashing, allows sample multiplexing and confident multiplet identification in high throughput scRNA-seq approaches. We have combined these methods to deeply profile the human immune system. We present an in-depth characterization of the human immune system using a panel of ~80 antibodies revealing complexity not previously observed by scRNA-seq. Finally, we present recent additions to the CITE-seq toolkit for additional single cell omics applications and compatibility with other single cell analysis platforms.