A method for monitoring a disease in a subject comprising: (a) generating one or more clonotype profiles from at least one sample obtained from the subject, wherein the at least one sample comprises T-cells and/or B-cells and is related to a first state of the disease, and wherein each clonotype profile is determined by a method comprising i. spatially isolating individual molecules of nucleic acid from said cells; ii. sequencing said spatially isolated individual molecules of nucleic acid by sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, or SOLiD sequencing, and iii. determining the levels of different sequences from said sample to generate said clonotype profile; (b) determining one or more correlating clonotypes of the disease in the subject based on the one or more clonotype profiles; and (c) monitoring the disease by determining the levels of the one or more correlating clonotypes in a subsequent sample obtained from the subject, wherein the levels of the one or more correlating clonotypes in the subsequent sample are determined by sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, or SOLiD sequencing. (a) generating one or more clonotype profiles from at least one sample obtained from the subject, wherein the at least one sample comprises T-cells and/or B-cells and is related to a first state of the disease, and wherein each clonotype profile is determined by a method comprising i. spatially isolating individual molecules of nucleic acid from said cells; ii. sequencing said spatially isolated individual molecules of nucleic acid by sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, or SOLiD sequencing, and iii. determining the levels of different sequences from said sample to generate said clonotype profile; i. spatially isolating individual molecules of nucleic acid from said cells; ii. sequencing said spatially isolated individual molecules of nucleic acid by sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, or SOLiD sequencing, and iii. determining the levels of different sequences from said sample to generate said clonotype profile; (b) determining one or more correlating clonotypes of the disease in the subject based on the one or more clonotype profiles; and (c) monitoring the disease by determining the levels of the one or more correlating clonotypes in a subsequent sample obtained from the subject, wherein the levels of the one or more correlating clonotypes in the subsequent sample are determined by sequencing by synthesis using reversibly terminated labeled nucleotides, pyrosequencing, 454 sequencing, allele specific hybridization to a library of labeled oligonucleotide probes, sequencing by synthesis using allele specific hybridization to a library of labeled clones that is followed by ligation, real time monitoring of the incorporation of labeled nucleotides during a polymerization step, polony sequencing, or SOLiD sequencing.